The goal is to investigate brain systems that mediate cognitive, affective, and reward[unreadable] processing in humans and to determine how these systems are influenced by late life depression, by[unreadable] genetic risk factors associated with depression, and by experimental manipulations of serotonin[unreadable] levels. Behavioral challenge tasks will be use during functional magnetic resonance imaging (fMRI) to[unreadable] investigate four specific aims: (1) We will complete studies initiated in the current funding period that[unreadable] investigate the influence of vascular lesions upon the interaction of ventral systems for emotional[unreadable] regulation and dorsal systems for executive control in patients with late life depression. These[unreadable] on-going studies also include an assessment of current clinical status, and whether treatment has[unreadable] led to a remission from depression. (2) We will characterize genetic influences upon the neural[unreadable] processing of emotional and rewarding stimuli using a task developed in current period that[unreadable] measures activity in amygdala, ventromedial and orbital frontal cortex, and ventral frontal cortex, and a[unreadable] second task that measures activity in striatal, midbrain, and dorsal systems associated with[unreadable] decisions about rewards. (3) We will evaluate the effects of neurotransmitter levels upon the neural[unreadable] processing of emotional and rewarding stimuli. Neuroimaging and neurophysiological studies[unreadable] reveal correlations between measures of neuronal activity and measures of behavioral states (e.g.,[unreadable] mood, decision preference, response time). Such correlations suggest functional relationships, but[unreadable] typically remain untested. To functionally probe the effects of emotional/reward systems upon[unreadable] executive processing systems, we will pharmacologically manipulate levels of the neurotransmitter[unreadable] serotonin using ATD. Observation of systematic shifts in mood, behavioral preferences, or sensitivity[unreadable] to reward outcomes would have profound implications for understanding phenotypic variation in[unreadable] behavior associated with conditions such as depression, addiction, and anxiety syndromes. (4) We[unreadable] will evaluate the effects of mood changes upon the neural processing of emotional and rewarding[unreadable] stimuli. A common consequence of depression is anhedonia, or the inability to derive pleasure (or[unreadable] other emotional reaction) from normally rewarding stimuli. We will use procedures developed in the[unreadable] current period to manipulate mood state over short time intervals, and we will investigate how[unreadable] transient negative mood influences activation in brain systems that process emotional and rewarding[unreadable] stimuli.